Background The coronavirus disease (COVID-19) epidemic has not been completely controlled. Although great achievements have been made in COVID-19 research and many antiviral drugs have shown good therapeutic effects against COVID-19, a simple oral antiviral drug for COVID-19 has not yet been developed. We conducted a meta-analysis to investigate the improvement in mortality or hospitalization rates and adverse events among COVID-19 patients with three new oral antivirals (including molnupiravir, fluvoxamine and Paxlovid). Methods We searched scientific and medical databases, such as PubMed, Web of Science, Embase and Cochrane Library for relevant articles and screened the references of retrieved studies on COVID-19. Results A total of eight studies were included in this study. The drug group included 2440 COVID-19 patients, including 54 patients who died or were hospitalized. The control group included a total of 2348 COVID-19 patients, including 118 patients who died or were hospitalized. The overall odds ratio (OR) of mortality or hospitalization was 0.33 (95% confidence interval [CI], 0.22–0.49) for COVID-19 patients in the drug group and placebo group, indicating that oral antiviral drugs were effective for COVID-19 patients and reduced the mortality or hospitalization by approximately 67%. Conclusions This study showed that three novel oral antivirals (molnupiravir, fluvoxamine and Paxlovid) are effective in reducing the mortality and hospitalization rates in patients with COVID-19. In addition, the three oral drugs did not increase the occurrence of adverse events, thus exhibiting good overall safety. These three oral antiviral drugs are still being studied, and the available data suggest that they will bring new hope for COVID-19 recovery and have the potential to be a breakthrough and very promising treatment for COVID-19. KEY MESSAGES Many antiviral drugs have shown good therapeutic effects, and there is no simple oral antiviral drug for COVID-19 patients. Meta-analysis was conducted for three new oral antivirals to evaluate the improvement in mortality or hospitalization rates and adverse events among COVID-19 patients. We focussed on three new oral Coronavirus agents (molnupiravir, fluvoxamine and Paxlovid) and hope to provide guidance for the roll-out of oral antivirals.

In cancer cells, loss of E-cadherin gene expression caused dysfunction of the cell-cell junction system, triggering cancer invasion and metastasis. Therefore, E-cadherin is an important tumor-suppressor gene. To understand how E-cadherin gene expression is regulated in cancer cells, we have used E-cadherin-positive and -negative expressing cells to find out the possible up-or downregulating transcription factors in human E-cadherin regulatory sequences. Functional analysis of human E-cadherin regulatory sequences constructs indicated that AML1, Sp1, and p300 may play important roles in promoting E-cadherin expression. In addition, we found there are four HNF3-binding sites in human E-cadherin regulatory sequences. The exogenous HNF3 can enhance the E-cadherin promoter activity in metastatic breast cancer cells and the metastatic breast cancer cells stably transfected with HNF3 showed re-expression of E-cadherin. The HNF3 stable transfectants changed from mesenchymal-like into epithelial morphology. The transwell assays showed the re-expressed E-cadherin reduced cell motility of metastatic breast cancer cells. These results suggested HNF3 may play important roles in the upregulation of the E-cadherin promoter, with the consequent re-expression of E-cadherin, thus reducing the metastatic potential of breast cancer cells. These findings suggested HNF3 plays important roles in the upregulation of the E-cadherin gene and may be able to reduce the motility of metastatic breast cancer cells.

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Aims Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. Methods We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data were then compared in benign and malignant tissues from the same organ/tissue using the student t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. Results We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (either in nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear), and twenty three organs/tissues show no significant difference in IHC score of any S1PR (cytoplasmic or nuclear) between benign and malignant changes. Conclusion This is the first study to evaluate the expression level of all S1PRs in benign and malignant tissues from multiple human organs. This study provides data regarding the systemic distribution, subcellular localization and differences in expression of all five S1PRs in benign and malignant changes for each organ/tissue.

Background: The coronavirus pneumonia is still spreading around the world. Much progress has been made in vaccine development, and vaccination will become an inevitable trend in the fight against this pandemic. However, the public acceptance of COVID-19 vaccination still remains uncertain.Methods: An anonymous questionnaire was used in Wen Juan Xing survey platform. All the respondents were divided into healthcare workers and non-healthcare workers. Multinomial logistic regression analyses were performed to identify the key sociodemographic, cognitive, and attitude associations among the samples of healthcare workers and non-healthcare workers.Results: A total of 2,580 respondents completed the questionnaire, including 1,329 healthcare workers and 1,251 non-healthcare workers. This study showed that 76.98% of healthcare workers accepted the COVID-19 vaccine, 18.28% workers were hesitant, and 4.74% workers were resistant. Among the non-healthcare workers, 56.19% workers received the COVID-19 vaccine, 37.57% workers were hesitant, and 6.24% workers were resistant. Among the healthcare workers, compared with vaccine recipients, vaccine-hesitant individuals were more likely to be female (AOR = 1.52, 95% CI: 1.12–2.07); vaccine-resistant individuals were more likely to live in the suburbs (AOR = 2.81, 95% CI: 1.44–3.99) with an income of 10,000 RMB or greater (AOR = 2.00, 95% CI: 1.03–3.90). Among the non-healthcare workers, vaccine-hesitant individuals were more likely to be female (AOR = 1.66, 95% CI: 1.31–2.11); vaccine-resistant individuals were also more likely to be female (AOR = 1.87, 95% CI: 1.16–3.02) and older than 65 years (AOR = 4.96, 95% CI: 1.40–7.62). There are great differences between healthcare workers and non-healthcare workers in their cognition and attitude toward vaccines.Conclusions: Our study shows that healthcare workers are more willing to be vaccinated than non-healthcare workers. Current vaccine safety issues continue to be a major factor affecting public acceptance, and to expand vaccine coverage in response to the COVID-19 pandemic, appropriate vaccination strategies and immunization programs are essential, especially for non-healthcare workers.

Aphids are infected with a wide variety of endosymbionts that can confer ecologically relevant traits. However, the bacterial communities of most aphid species are still poorly characterized. This study investigated the bacterial diversity of the cotton aphid Aphis gossypii associated with Bt cotton in northern China by targeting the V4 region of the 16S rDNA using the Illumina MiSeq platform. Our sequencing data revealed that bacterial communities of A. gossypii were generally dominated by the primary symbiont Buchnera, together with the facultative symbionts Arsenophonus and Hamiltonella. To our knowledge, this is the first report documenting the facultative symbiont Hamiltonella in A. gossypii. Moreover, the bacterial community structure was similar within aphids from the same province, but distinct among those from different provinces. The taxonomic diversity of the bacterial community is greater in Hebei Province compared with in samples from Henan and Shandong Provinces. The selection pressure exerted by the different geographical locations could explain the differences found among the various provinces. These findings broaden our understanding of the interactions among aphids, endosymbionts and their environments, and provide clues to develop potential biocontrol techniques against this cotton aphid.

BackgroundThe cotton-melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a polyphagous species with a worldwide distribution and a variety of biotypes. North China is a traditional agricultural area with abundant winter and summer hosts of A. gossypii. While the life cycles of A. gossypii on different plants have been well studied, those of the biotypes of North China are still unclear.ResultsHost transfer experiments showed that A. gossypii from North China has two host-specialized biotypes: cotton and cucumber. Based on complete mitochondrial sequences, we identified a molecular marker with five single-nucleotide polymorphisms to distinguish the biotypes. Using this marker, a large-scale study of biotypes on primary winter and summer hosts was conducted. All A. gossypii collected from three primary hosts—hibiscus, pomegranate, and Chinese prickly ash—were cotton biotypes, with more cotton-melon aphids found on hibiscus than the other two species. In May, alate cotton and cucumber biotypes coexisted on cotton and cucumber seedlings, but each preferred its natal host. Both biotypes existed on zucchini, although the cucumber biotype was more numerous. Aphids on muskmelon were all cucumber biotypes, whereas most aphids on kidney bean were cotton biotypes. Aphids on seedlings of potato and cowpea belong to other species. In August, aphids on cotton and cucumber were the respective biotypes, with zucchini still hosting both biotypes as before. Thus, the biotypes had different fitnesses on different host plants.ConclusionsTwo host-specialized biotypes (cotton and cucumber) are present in North China. Hibiscus, pomegranate, and Chinese prickly ash can serve as winter hosts for the cotton biotype but not the cucumber biotype in North China. The fitnesses of the two host-specialized biotypes differ on various summer hosts. When alate aphids migrate to summer hosts, they cannot accurately land on the corresponding plant.